Participation of lipids in the tumor response to photodynamic therapy and its exploitation for therapeutic gain.

IF 5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mladen Korbelik, Michal Heger, Albert W Girotti
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引用次数: 0

Abstract

Hydroperoxides of unsaturated membrane lipids (LOOHs) are the most abundant non-radical intermediates generated by photodynamic therapy (PDT) of soft tissues such as tumors and have far longer average lifetimes than singlet oxygen or oxygen radicals formed during initial photodynamic action. LOOH-initiated post-irradiation damage to remaining membrane lipids (chain peroxidation) or to membrane-associated proteins remains largely unrecognized. Such after-light processes could occur during clinical oncological PDT, but this is not well-perceived by practitioners of this therapy. In general, the pivotal influence of lipids in tumor responses to PDT needs to be better appreciated. Of related importance is the fact that most malignant tumors have dramatically different lipid metabolism compared with healthy tissues, and this is often ignored. The response of tumors to PDT appears especially vulnerable to manipulations within the tumor lipid microenvironment. This can be exploited for therapeutic gain with oncological PDT, as exemplified here by the combined treatment with antitumor lipid edelfosine.

不饱和膜脂的氢过氧化物(LOOHs)是对肿瘤等软组织进行光动力疗法(PDT)时产生的最丰富的非自由基中间产物,其平均寿命远远长于最初光动力作用时形成的单线态氧或氧自由基。LOOH 引发的辐照后对剩余膜脂质(膜链过氧化)或膜相关蛋白质的损伤在很大程度上仍未被认识到。在临床肿瘤光动力疗法中可能会出现这种光照后过程,但这种疗法的从业人员对此认识不足。总的来说,脂质在肿瘤对光化学疗法反应中的关键影响需要得到更好的认识。与此相关的一个重要事实是,与健康组织相比,大多数恶性肿瘤的脂质代谢有很大的不同,而这一点往往被忽视。肿瘤对光化学疗法的反应似乎特别容易受到肿瘤脂质微环境操纵的影响。肿瘤光导透射疗法可以利用这一点获得治疗效果,与抗肿瘤脂质依地福辛的联合治疗就是一例。
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来源期刊
Journal of Lipid Research
Journal of Lipid Research 生物-生化与分子生物学
CiteScore
11.10
自引率
4.60%
发文量
146
审稿时长
41 days
期刊介绍: The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.
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